Over 30 million people are infected with HIV worldwide, and 2.5 to 3 million new infections have been estimated to occur yearly. Although effective antiretroviral therapies are available, millions succumb to AIDS every year, especially in sub-Saharan Africa, underscoring the need to develop measures to prevent the spread of this disease.
An enveloped virus, HIV-1 hides from humoral recognition behind a wide array of protective mechanisms. The major envelope protein of HIV-1 is a glycoprotein of approximately 160 kD (gp160). During infection proteases of the host cell cleave gp160 into gp120 and gp41. gp41 is an integral membrane protein, while gp120 protrudes from the mature virus. Together gp120 and gp41 make up the HIV envelope spike, which is a target for neutralizing antibodies.
Adjuvants modulate the immune response and can improve the immunogenicity of vaccine candidates. The oil in water emulsion MF59 has been proposed to replace Alum in a Phase IIb trial in South Africa using ALVAC-HIV/gp120 vaccines. Unlike the Th2-inducing adjuvant Alum, MF59 induces both Th1 and Th2 responses, increases local inflammation, and can alter the generation of antibody isotypes, in an antigen dependent manner (Ott et al., Vaccine 13, 1557-1562 (1995); Carlson et al., Am. J. Pathol. 156, 2057-2065 (2000); Mosca et al. Proc. Natl. Acad. Sci. U.S.A 105, 10501-10506 (2008); Caproni, E. et al., J. Immunol. 188, 3088-3098 (2012); Valensi et al., J. Immunol. 153, 4029-4039 (1994)). The adjuvant MF59 increased the effectiveness of influenza vaccines, by enhancing antibody responses in the elderly (Podda, Vaccine 19, 2673-2680 (2001)) and in children (Vesikari et al., Pediatr. Infect. Dis. J. 28, 563-571 (2009)) when compared to other adjuvants. MF59, given with Hepatitis B virus vaccines, increased the generation and durability of protective antibodies in primates, mice, and immunosuppressed individuals (Traquina, et al., J. Infect. Dis. 174, 1168-1175 (1996): Singh, et al., Vaccine 24, 1680-1686 (2006)).
Immunogenicity studies conducted in humans suggest that the use of the MF59 instead of the Alum could benefit HIV vaccines. A Phase I clinical trial showed that the MF59 given together with a gp120/HIV-1SF2 HIV protein vaccine candidate was superior to Alum in inducing HIV-specific immune responses (McElrath, Semin. Cancer Biol. 6, 375-385 (1995)) Two Phase I/II trials demonstrated increased immune responses when an ALVAC-primed response was boosted with protein formulated in MF59 compared to Alum (Nitayaphan et al., J. Infect. Dis. 190, 702-706 (2004); Thongcharoen et al. J. Acquir. Immune. Defic. Syndr. 46, 48-55 (2007). However, a need remains for adjuvants that can be used to increase the immune response to HIV immunogens. In addition, a need remains for assays to determine if an immunogenic composition, such as a vaccine, will be effective for inducing an immune response to HIV in a subject.